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At least 37 records · Page 2

Validation of Spectral Analysis as a Noninvasive Tool to Assess Autonomic Regulation of Cardiovascular Function

A major focus of our program has been to develop a sensitive noninvasive procedure to quantify early weightlessness-induced changes in cardiovascular function or potential dysfunction. Forty studies of healthy young volunteers (10 men and 10 women, each studied twice) were conducted to determine changes in the sympatho-vagal balance of autonomic control of cardiovascular regulation during graded headward and footward blood volume shifts. Changes in sympatho-vagal balance were classified by changes in the mean levels and spectral content of cardiovascular variables and verified by changes in circulating levels of catecholamines and pancreatic polypeptide. Possible shifts in intra/extravascular fluid were assessed from changes in hematocrit and plasma mass density while changes in the stimulus to regulate plasma volume were determined from Plasma Renin Activity (PRA). Autonomic blockade was used to unmask the relative contribution of sympathetic and parasympathetic efferent influences in response to 10 min each of 0, 20 and 40 mmHg Lower Body Negative Pressure (LBNP) and 15 and 30 mmHg Positive Pressure (LBPP). The combination of muscarinic blockade with graded LBNP and LBPP was used to evoke graded increases and decreases in sympathetic activity without parasympathetic contributions. The combination of beta blockade with graded LBNP and LBPP was used to produce graded increases and decreases in parasympathetic activity without beta sympathetic contributions. Finally, a combination of both beta and muscarinic blockades with LBNP and LBPP was used to determine the contribution from other, primarily alpha adrenergic, sources. Mean values, spectral analyses and time frequency analysis of R-R interval (HR), Arterial Pressure (AP), peripheral blood flow (RF), Stroke Volume (SV) and peripheral resistance (TPR) were performed for all phases of the study. Skin blood Flow (SF) was also measured in other studies and similarly analyzed. Spectra were examined for changes in three frequency regions (low 0.006 - 0.005 Hz (LF), mid 0.05 - 0.15 Hz (W), and high 0.15 - 0.45 Hz (EF)). The primary objective of the study was to indicate which changes in the mean values and/or spectra of cardiovascular variables consistently correlated with changes in sympatho-vagal balance in response to headward and footward fluid shifts. A secondaey objective was to quantify the vascular and extravascular fluid shifts evoked by LBNP and LBPP. The principal hypothesis being tested was that headward fluid shifts would evoke an increase in parasympathetic activity and footward fluid shifts would evoke an increase in sympathetic activity both of which would be detected by spectral analysis and verified by circulating hormones. Hematocrit (HCT), plasma mass density and plasma renin activity increased with muscarinic blockade and with LBNP, a response indicative of a plasma shift to extravascular spaces. Beta blockade alone or after muscarinic blockade had no effect on HCT or plasma mass density. With respect to intravascular fluid volume distribution, LBNP and LBPP produced sufficient upper body vascular fluid shifts to evoke appropriate autonomic regulatory responses.

Knapp, Charles F.

A new method for culturing Plasmodium falciparum shows replication at the highest erythrocyte densities

Plasmodium falciparum replicates poorly in erythrocyte densities greater than a hematocrit of 20%. A new method to culture the major malaria parasite was developed by using a hollow fiber bioreactor that preserves healthy erythrocytes at hematocrit up to 100%. P. falciparum replicated equally well at all densities studied. This method proved advantageous for large-scale preparation of parasitized erythrocytes (and potentially immunogens thereof), because high yields ( approximately 10(10) in 4 days) could be prepared with less cost and labor. Concomitantly, secreted proteins were concentrated by molecular sieving during culture, perhaps contributing to the parasitemic limit of 8%-12% with the 3D7 strain. The finding that P. falciparum can replicate at packed erythrocyte densities suggests that this system may be useful for study of the pathogenesis of fatal cerebral malaria, of which one feature is densely packed blood cells in brain microvasculature.

Plasmodium falciparum/growth & development

Visualizing ultrasound through computational modeling

The Doppler Ultrasound Hematocrit Project (DHP) hopes to find non-invasive methods of determining a person s blood characteristics. Because of the limits of microgravity and the space travel environment, it is important to find non-invasive methods of evaluating the health of persons in space. Presently, there is no well developed method of determining blood composition non-invasively. This projects hopes to use ultrasound and Doppler signals to evaluate the characteristic of hematocrit, the percentage by volume of red blood cells within whole blood. These non-invasive techniques may also be developed to be used on earth for trauma patients where invasive measure might be detrimental. Computational modeling is a useful tool for collecting preliminary information and predictions for the laboratory research. We hope to find and develop a computer program that will be able to simulate the ultrasound signals the project will work with. Simulated models of test conditions will more easily show what might be expected from laboratory results thus help the research group make informed decisions before and during experimentation. There are several existing Matlab based computer programs available, designed to interpret and simulate ultrasound signals. These programs will be evaluated to find which is best suited for the project needs. The criteria of evaluation that will be used are 1) the program must be able to specify transducer properties and specify transmitting and receiving signals, 2) the program must be able to simulate ultrasound signals through different attenuating mediums, 3) the program must be able to process moving targets in order to simulate the Doppler effects that are associated with blood flow, 4) the program should be user friendly and adaptable to various models. After a computer program is chosen, two simulation models will be constructed. These models will simulate and interpret an RF data signal and a Doppler signal.

Guo, Theresa W.

Exercise Increases the Cardiovascular Stimulus Provided by Artificial Gravity

We investigated fluid shifts and regulatory responses to variations of posture, exercise, Gz level and radius of rotation in subjects riding NASA Ames 20G centrifuge. Results are from 4 protocols that address radius and exercise effects only. Protocol A: After 10 min supine control, 12 healthy men (35 plus or minus 9 yr, 82.8 plus or minus 7.9 kg) were exposed to rotational 1 Gz (2.5 m radius) for 2 min followed by 20 min alternating between 1 and 1.25 Gz. Blood samples were taken pre and post spin. Protocol B: Same as A, but lower limb exercise (70% V02max) preceded ramps to 1.25 Gz. Protocol C: Same as A but radius of rotation 8.3 m. Protocol D: Same as B but at 8.3 m. The 8 subjects who completed all protocols, increased heart rate (HR) from control, on average, by: A: 5, B: 39, C: 11, D: 44 bpm. For thoracic fluid volume, (bioimpedance), the 8 subjects changed from control, on average: A: -394, B: -548, C: -537, D: -708 mL. For thigh fluid volume, changes from control, on average, were: A: -137, B: 129, C: -75, D: 159 mL. Hematocrit changes from control were: A: 2.3, B: 3.5, C: 2.3, D: 4.3 %. Radius effects were mild and included greater loss of fluid from the thorax, less fluid loss from the thigh and increased heart rate at the longer radius. Pre-acceleration exercise effects were more dramatic and included additional loss of fluid from the chest, increased fluid volume of the thigh, increased hematocrit and greater heart rate increases. We propose that short bouts of intense exercise can be used to magnify the cardiovascular stress delivered by artificial gravity (AG) training and the combination of AG with exercise training can be fine-tuned to preserve orthostatic tolerance of astronauts during spaceflight.

Howarth, M. S.

Blood studies

Blood cell counts, hematocrits, and hemoglobin concentrations of subjects exposed to pure oxygen environment

HEMATOCRIT

Dose and dose rate effects of whole-body proton-irradiation on lymphocyte blastogenesis and hematological variables: part II

The goal of part II of this study was to evaluate functional characteristics of leukocytes and circulating blood cell parameters after whole-body proton irradiation at varying doses and at low- and high-dose-rates (LDR and HDR, respectively). C57BL/6 mice (n=51) were irradiated and euthanized at 4 days post-exposure for assay. Significant radiation dose- (but not dose-rate-) dependent decreases were observed in splenocyte responses to T and B cell mitogens when compared to sham-irradiated controls (P<0.001). Spontaneous blastogenesis, also significantly dose-dependent, was increased in both blood and spleen (P<0.001). Red blood cell counts, hemoglobin concentration, and hematocrit were decreased in a dose-dependent manner (P<0.05), whereas thrombocyte numbers were only slightly affected. Comparison of proton- and gamma-irradiated groups (both receiving 3 Gy at HDR) showed a higher level of spontaneous blastogenesis in blood leukocytes and a lower splenocyte response to concanavalin A following proton irradiation (P<0.05). There were no dose rate effects. Collectively, the data demonstrate that the measurements in blood and spleen were largely dependent upon the total dose of proton radiation and that an 80-fold difference in the dose rate was not a significant factor. A difference, however, was found between protons and gamma-rays in the degree of change induced in some of the measurements.

Non-NASA Center

Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

NASA Discipline Radiation Health

Neocytolysis on descent from altitude: a newly recognized mechanism for the control of red cell mass

BACKGROUND: Studies of space-flight anemia have uncovered a physiologic process, neocytolysis, by which young red blood cells are selectively hemolyzed, allowing rapid adaptation when red cell mass is excessive for a new environment. OBJECTIVES: 1) To confirm that neocytolysis occurs in another situation of acute plethora-when high-altitude dwellers with polycythemia descend to sea level; and 2) to clarify the role of erythropoietin suppression. DESIGN: Prospective observational and interventional study. SETTING: Cerro de Pasco (4380 m) and Lima (sea level), Peru. PARTICIPANTS: Nine volunteers with polycythemia. INTERVENTIONS: Volunteers were transported to sea level; three received low-dose erythropoietin. MEASUREMENTS: Changes in red cell mass, hematocrit, hemoglobin concentration, reticulocyte count, ferritin level, serum erythropoietin, and enrichment of administered(13)C in heme. RESULTS: In six participants, red cell mass decreased by 7% to 10% within a few days of descent; this decrease was mirrored by a rapid increase in serum ferritin level. Reticulocyte production did not decrease, a finding that establishes a hemolytic mechanism.(13)C changes in circulating heme were consistent with hemolysis of young cells. Erythropoietin was suppressed, and administration of exogenous erythropoietin prevented the changes in red cell mass, serum ferritin level, and(13)C-heme. CONCLUSIONS: Neocytolysis and the role of erythropoietin are confirmed in persons with polycythemia who descend from high altitude. This may have implications that extend beyond space and altitude medicine to renal disease and other situations of erythropoietin suppression, hemolysis, and polycythemia.

Non-NASA Center

Hormonal and electrolyte responses to acute isohemic volume expansion in unanesthetized rats

This study was undertaken to explore the time course of the metabolic response to isohemic blood volume expansion (30%) in normotensive, unanesthetized Sprague-Dawley rats. Whole blood, drawn from a femoral artery catheter of conscious donor rats, was infused into the jugular vein of recipient rats. Blood samples were drawn from a carotid artery of recipient rats at time points beginning immediately post-volume expansion (IPVE) up through 5 days post-volume expansion (PVE). To characterize the attendant compensatory mechanisms, the plasma concentrations of electrolytes and fluid regulatory hormones were determined. Hematocrit began to raise IPVE and was significantly elevated above control IPVE 20, 30, 40, 60, and 90 min, and 2, 4, 6, 8, 12, and 24 hr PVE. Consistent with our current understanding of the hormonal response to excess volume, atrial natriuretic factor was significantly increased above the prevolume expansion (control) values 0-30 min PVE. Surprisingly, plasma aldosterone levels were significantly increased above control at 20 and 30 min and 6 hr PVE, whereas plasma renin activity was significantly decreased 30-40 min PVE. Plasma sodium was not changed from control values except for a significant increase at 6 hr post-volume expansion. Plasma potassium, osmolality, and arginine vasopressin levels were not altered by the volume expansion. These studies delineate the physiologic time scheme operative in the regulation of fluid volume during acute ischemic volume expansion.

NASA Discipline Cardiopulmonary

Renal and cardiovascular responses to water immersion in trained runners and swimmers

The purpose of this study was to determine if fluid-electrolyte, renal, hormonal, and cardiovascular responses during and after multi-hour water immersion were associated with aerobic training. Additionally, we compared these responses in those who trained in a hypogravic versus a 1-g environment. Seventeen men comprised three similarly aged groups: six long-distance runners, five competitive swimmers, and six untrained control subjects. Each subject underwent 5 h of immersion in water [mean (SE)] 36.0 (0.5) degrees C to the neck. Immediately before and at each hour of immersion, blood and urine samples were collected and analyzed for sodium (Na), potassium, osmolality, and creatinine (Cr). Plasma antidiuretic hormone and aldosterone were also measured. Hematocrits were used to calculate relative changes in plasma volume (% delta Vpl). Heart rate response to submaximal cycle ergometer exercise (35% peak oxygen uptake) was measured before and after water immersion. Water immersion induced significant increases in urine flow, Na clearance (CNa), and a 3-5% decrease in Vpl. Urine flow during immersion was greater (P < 0.05) in runners [2.4 (0.4) ml.min-1] compared to controls [1.3 (0.1) ml.min-1]. However, % delta Vpl, CCr, CNa and CH2O during immersion were not different (P > 0.05) between runners, swimmers, and controls. After 5 h of immersion, there was an increase (P < 0.05) in submaximal exercise heart rate of 9 (3) and 10 (3) beats.min-1 in both runners and controls, respectively, but no change (P > 0.05) was observed in swimmers.(ABSTRACT TRUNCATED AT 250 WORDS).

Running/physiology

Exogenous erythropoietin increases hematological status, fat oxidation, and aerobic performance in males following prolonged strenuous training

Abstract This study investigated the effects of EPO on hemoglobin (Hgb) and hematocrit (Hct), time trial (TT) performance, substrate oxidation, and skeletal muscle phenotype throughout 28 days of strenuous exercise. Eight males completed this longitudinal controlled exercise and feeding study using EPO (50 IU/kg body mass) 3×/week for 28 days. Hgb, Hct, and TT performance were assessed PRE and on Days 7, 14, 21, and 27 of EPO. Rested/fasted muscle obtained PRE and POST EPO were analyzed for gene expression, protein signaling, fiber type, and capillarization. Substrate oxidation and glucose turnover were assessed during 90‐min of treadmill load carriage (LC; 30% body mass; 55 ± 5% V̇O 2 peak) exercise using indirect calorimetry, and 6‐6‐[ 2 H 2 ]‐glucose PRE and POST. Hgb and Hct increased, and TT performance improved on Days 21 and 27 compared to PRE ( p < 0.05). Energy expenditure, fat oxidation, and metabolic clearance rate during LC increased ( p < 0.05) from PRE to POST. Myofiber type, protein markers of mitochondrial biogenesis, and capillarization were unchanged PRE to POST. Transcriptional regulation of mitochondrial activity and fat metabolism increased from PRE to POST ( p < 0.05). These data indicate EPO administration during 28 days of strenuous exercise can enhance aerobic performance through improved oxygen carrying capacity, whole‐body and skeletal muscle fat metabolism.

Drummer, Devin J.

Metabolic effects of artificial environments

The mechanisms by which inert gases influence metabolism were investigated from several viewpoints. Groups of rats were exposed at the thermal neutral temperature of the respective mixtures, to normoxic (P sub A 02 = 100 mm Hq) environments with argon, helium or nitrogen as the diluent at a total pressure of one atmosphere. The possible influence of diluent gases on oxygen transport to the cell was examined with hypoxic (P sub A O2 = 70 mm Hg) mixtures of the same diluent gases. Metabolic measurements included food, water, and oxygen consumption, CO2 production, hematocrit and the rate C-14O2 of expiration subsequent to intraperitoneal injection of acetate-1-C-14 or glucose UL-C-14. Argon-exposed animals showed a consistently decreased metabolic rate while, on the other hand, helium-exposed rats did not significantly alter metabolic rate relative to nitrogen. Certain indices, including acetate and glucose utilization, suggested that helium attenuated the imposed hypoxia at the cellular level while argon facilitated it as compared with nitrogen. These results suggest that metabolic influence of helium is largely thermal in nature while argon has a significant direct metabolic effect and that diluent gases may selectively influence oxygen availability to the interior of the cell.

Jordan, J. P.

Passenger fluid volumes measured before and after a prolonged commercial jet flight.

Interstitial and intracellular fluid volumes were calculated from measured plasma volume, extracellular volume and total body water of six subjects before and after a 24-hour commercial overseas flight. No change occurred in these spaces or in peripheral hematocrit or total serum protein concentration. The subjective feeling of dehydration and the actual swelling of the lower extremities characteristically found among passengers at the end of a long trip of this type seems to represent a shift in body fluids to the dependent portions of the body rather than water retention or a decrease in the intravascular water volume.

Johnson, P. C.

Neuropathological evaluation of monkeys exposed to body-alone X-radiation.

Investigation of the problem of whether morphological changes occurring in the central nervous system (CNS) following whole-body irradiation are attributable in part to abscopal factors. The 12 monkeys irradiated and the 6 that served as controls were chosen from a pool of 25 young monkeys. Over the postirradiation survival period of 14 days the hematocrit and hemoglobin values varied only slightly from the baseline values and from the values in the 6 control animals. White cell fractions were reduced in quantity but tended to recover relatively soon after irradiation. The design of this experiment was regarded as adequate to allow a conclusion whether pathological changes in the CNS of the irradiated animals differed from or exceeded those observed in the control animals. That such occurred on both counts in 3 of the 12 irradiated animals was evident. It appears that all the lesions must have been abscopally induced.

Haymaker, W.